Endogenous polyamine function—the RNA perspective

Abstract

Recent progress with techniques for monitoring RNA structure in cells such as ‘DMS-Seq’ and ‘Structure-Seq’ suggests that a new era of RNA structure-function exploration is on the horizon. This will also include systematic investigation of the factors required for the structural integrity of RNA. In this context, much evidence accumulated over 50 years suggests that polyamines play important roles as modulators of RNA structure. Here, we summarize and discuss recent literature relating to the roles of these small endogenous molecules in RNA function. We have included studies directed at understanding the binding interactions of polyamines with polynucleotides, tRNA, rRNA, mRNA and ribozymes using chemical, biochemical and spectroscopic tools. In brief, polyamines bind RNA in a sequence-selective fashion and induce changes in RNA structure in context-dependent manners. In some cases the functional consequences of these interactions have been observed in cells. Most notably, polyamine-mediated effects on RNA are frequently distinct from those of divalent cations (i.e. Mg2+) confirming their roles as independent molecular entities which help drive RNA-mediated processes.

Spermine Condenses DNA, but Not RNA Duplexes

“…Spermine bound deep in the major grooves stabilizes mixed-sequence RNA One of spermine's many functions is to stabilize the structure of RNA (2,6,21), and this stabilization has many important repercussions. For example, spermine-induced stabilization of tRNA prevents incorrect basepairing and increases the fidelity of translation (21), and the resulting binding and stabilization also create binding sites for divalent cations (61).…”

“…Spermine is a tetravalent polyamine that is found in high concentrations in cells (1)(2)(3). It interacts with nucleic acids in diverse and important ways, functioning as a protective agent (4)(5)(6)(7)(8) and a modulator of DNA secondary structure (9).…”

“…It interacts with nucleic acids in diverse and important ways, functioning as a protective agent (4)(5)(6)(7)(8) and a modulator of DNA secondary structure (9). In cells, spermine is largely bound to RNA, with between one and four bound spermine molecules per 100 RNA phosphates (2,10) (between 65% and 85% of the total spermine (9)). Crystal structures of spermine complexed with tRNA show spermine lying deep within the major groove (11).…”

“…Such condensation would lead to aggregation instead of ordered folding and could potentially interfere with important RNA functions. However, given that spermine plays roles in processes that could be impeded by condensation, such as mRNA translation (2), tRNA aminoacylation, and the formation of correct tRNA-ribosome interactions (21), it appears that spermine-induced RNA condensation may not occur in vivo. A correct and thorough understanding of spermine-RNA interactions could provide insight into whether spermine causes RNA condensation and how it facilitates the above key processes.…”

Speculation: Polyamines are important in abiotic stress signaling

“…They can bind to the phospholipid head groups of membranes influencing their permeability characteristics. They can also bind to various proteins non-specifically, stabilizing their structure and resulting in changes in their activity and/or function, as well as to chromatin, causing an alteration in the availability of genomic sites to DNA or RNA polymerases, leading to altered DNA and RNA synthesis [2]. There are several lines of evidence supporting the relationship between polyamines and photosynthesis.…”